Effect of septohippocampal lesions on thyrotropin-releasing hormone antagonism of pentobarbital narcosis.
Thyrotropin-releasing hormone (TRH) has been shown to antagonize pentobarbital narcosis in a variety of mammalian phylogeny, and many lines of evidence indicate that TRH action in the septum to modulate the septohippocampal system may be the neuroanatomical substrate mediating this effect. To further examine this hypothesis, the analeptic response following injection of TRH into the lateral ventricles or ventromedial septum was measured after lesions of the septum, fimbria or hippocampus. Lesions were induced using either radiofrequency current, aspiration or  microinjection of kainic acid. Bilateral electrolytic lesions of the fimbria were found to block the antagonism of pentobarbital narcosis by intraseptal injection of 500 ng TRH, indicating that intraseptal TRH is acting via the septohippocampal system. In contrast, complete aspiration of the dorsal hippocampi did not attenuate intracerebroventricular (i.c.v.) administration of TRH. However, large electrolytic septal lesions effectively blocked i.c.v. TRH. These findings indicate first that i.c.v. TRH can cause arousal from pentobarbital narcosis via interaction with alternative neuroanatomical substrates from the septohippocampal system, and secondly, that these alternative substrates have axons which either synapse in or pass through the septum. The fact that injection of kainic acid into the ventromedial septum did not antagonize i.c.v. TRH supports the likelihood that the effectiveness of electrolytic septal lesions results from disruption of fibers in passage and not destruction of neuron perikarya in the septum.
D000768:Anesthesia, General; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*
D013973:Thyrotropin-Releasing Hormone; D010424:Pentobarbital; D007608:Kainic Acid